The long-term goal is to understand the function and regulation of genes that are involved in heart development and to elucidate the molecular basis of cardiac differentiation, morpho-genesis and function. Particular emphasis will be placed on the role of the homeobox gene, tinman, during these processes in Drosophila. Drosophila cardiogenesis has become an excellent model for studying the genetic mechanisms that determine the initial phases of heart development in vertebrates, and for finding crucial factors involved in these processes. It is the first system in which the gene network responsible for specifying and positioning the cardiac mesoderm, the tissue that will form the heart, has been characterized in significant detail. As a result, remarkably similarities in molecular mechanisms have been discovered between drosophila and vertebrate heart development, strongly supporting an evolutionary conservation of heart development between insects (Drosophila) and vertebrate. Because of tinman's principal role in heart development, we plan to further elucidate its function and regulation (Aim 1). In a molecular screen, we further propose to identify transacting factors that are necessary for cardiac tinman expression, which is likely to yield new players in heart development (Aim 2), and in addition, may lead to new parallel mechanisms in vertebrate cardiogenesis. In a genetic screen, we further plan to identify new gene functions that are in control of and participate during cardiac differentiation and physiological function (Aim 3). We believe that the proposed research will again serve as a prototype for studying the genetic basis of cardiac differentiation, which already has helped (eg. Schott et al., 1998) and will continue to help to understand the molecular basis of congenital heart disease.